MDM2 and hepatocellular carcinoma: However, targeting MDM2 presented certain difficulties particularly in the context of HCC, as the liver tissue appears to be relatively insensitive to alterations in MDM2—liver tissue remains phenotypically normal after MDM2 ablation, while colon and bone marrow tissues undergo potent apoptosis, suggesting that the MDM2-dependent deactivation of p53wt may vary across organs [17, 18].